scholarly journals P674 Monitoring posologic change in adalimumab intensification dosing regimen from 40 mg every week to 80 mg every other week

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S551-S552
Author(s):  
M T Diz Lois Palomares ◽  
Á Porta Sánchez ◽  
L Elberdin Pazos ◽  
B González Conde ◽  
M Outeda Macías ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Median Time ◽  
Patient Comfort ◽  
Pharmacokinetic Studies ◽  
Dosing Regimen ◽  
First Line ◽  
Mayo Score ◽  
Previous Regimen ◽  
Original Laboratory ◽  
Trough Levels

Abstract Background The previous usual adalimumab (ADA) intensification regimen was 40 mg every week (ew)). Recently the original laboratory commercialised the 80 mg injection pen, with pharmacokinetic studies indicating an alternative intensification dose of 80 mg every other week (eow) similar to 40 mg ew, even though interchangeability has not been assessed in clinical practice. In the biosimilars era, this pen was sold to many Hospitals at the same price as the 40mg pen. For this fact and for patient comfort, we proposed our stable-intensificated-ADA IDB patients on a 40 mg ew regimen, to change the dose to 80 mg eow (clinical practice). Methods In this setting, we designed an observational study to monitor clinical, analytical and pharmacokinetic outcomes through this posologic change, for patients who signed the Informed Consent. Clinical (Harvey–Bradshaw index (HBI), partial Mayo score), analytic parameters and ADA trough levels were prospectively obtained at baseline, 4 and 8 months after posologic change. We describe the evolution of this cohort and calculate savings. Results 12 from 18 patients initially evaluated for new dose regimen were finally changed. All of them agreed to participate in the study. Eighty-three per cent were CD patients, 58% males, median age 51 years old (intecuartil range (IQR) 42–55). Median age at IBD diagnosis was 34 years (IQR 24–44). In 9 patients ADA was the first-line biologic. Median IBD duration before starting ADA was 6 years (IQR 5–8). Median time from ADA initiation to intensification was 31 months (IQR 14–55). The median time of ADA intensification was 37 months (IQR 30–66). Seventy per cent of patients were on immunosuppressors (IS) at the start of the study. Table 1 shows the results of clinical, analytical variables and ADA trough levels at baseline, 4 and 8 months. No differences were found. At 4 months, all patients maintained ADA 80 mg eow. Two patients referred mild worsening, (HBI from 3–4 to 5–6) without significant changes in CRP, calprotectin or ADA levels. They recovered after restoring the previous regimen (ADA 40mg ew). At 8 months, ADA was stopped in one patient in remission with undetectable ADA levels and positive ATI. Total savings in the first 8 months were 59022 €. Conclusion in IBD patients with stable response to ADA intensification regimen of 40 mg ew, changing to 80mg eow seems to maintain response and similar trough levels, although some patients may perceive mild symptoms. Economic savings are 50% per patient.

Cefepime Dosing in Neonates: What is the Evidence?

2019 ◽  
Author(s):  
Danielle McDonald ◽  
Pooja Shah
Keyword(s):  
Clinical Practice ◽  
English Language ◽  
Inhibitory Concentration ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Serum Concentrations ◽  
Dosing Regimen ◽  
Dosing Interval ◽  
Dosing Frequency ◽  
Dosing Strategies

Abstract Objective Recommended cefepime dosing strategies in neonates varies in commonly utilized dosing references with regard to dose and frequency. The objective of this review is to summarize and evaluate the available literature describing cefepime dosing in neonatal patients. Study Design We performed a literature review in MEDLINE using the keyword cefepime. The search was limited to the English language, humans, and patients <2 months of age. We evaluated four pharmacokinetic studies and two studies describing the use of cefepime in clinical practice. Results The available studies assessing cefepime serum concentrations in neonatal patients demonstrated maintenance of adequate pharmacokinetic parameters when utilizing a dosing frequency of every 12 hours, specifically for organisms with a minimum inhibitory concentration (MIC) ≤ 8 mg/L. In studies evaluating clinical outcomes of cefepime use in neonates, the most frequent adverse effects reported included seizures and hypophosphatemia. Microbiologic cure was demonstrated with a dosing regimen of 50 mg/kg per dose every 12 hours. Conclusion Cefepime dosed 30 to 50 mg/kg per dose every 12 hours may be appropriate to achieve a concentration two to four times above an MIC ≤ 8 mg/L for at least 60% of the dosing interval in neonatal patients.

scholarly journals Treatment-Free Remission (TFR) Is Feasible in Clinical Practice Latin-America (LA): A Real-World Cohort of Patients in Colombia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4605-4605
Author(s):  
Virginia Abello ◽  
Isabel Munevar ◽  
Rigoberto Gomez ◽  
Monica Osuna Pérez ◽  
Carlos Daniel Bermudez Silva ◽  
...  
Keyword(s):  
Health Care ◽  
Clinical Practice ◽  
Median Time ◽  
Health Care System ◽  
Real World ◽  
Research Funding ◽  
Chronic Phase ◽  
First Line ◽  
Number Of Patients ◽  
Care System

Abstract BACKGROUND: Long-term Tirosin Kinase Inhibitor (TKI) treatment is related to notable adverse events, quality-of-life impact and significant costs to health systems. Many patients in optimal response are candidates to TKI discotinuation that has proven to be safe in clinical trials. TFR has become a new goal for CML management. Information about its implementation in clinical practice in LA is limited. The aim of this study is to describe the results, safety and assess the possible economic impact of a cohort of patients that has discontinued TKI in clinical practice in Colombia. MATERIAL AND METHODS : The Colombian Association of Hematology and Oncology (ACHO)'s hematological disease registry (RENEHOC) is a multicenter nationwide registry on hematologic malignancies that captures information from 18 academic and general community centers with Institutional Ethics Committee approval, since 2018. Since 2019, it has been collecting information on CML. This report represents a sub-analysis of CML patients in the registry in whom discontinuation was performed. Treatment was according to investigator preferences. A total of 449 CML adult patients treated in the last 20 years have been registered until now on RENEHOC. 29 patients were considered eligible for TFR; in 27 of them, TKI have been discontinued. The main outcome measured is survival without TKI re-initiation. RESULTS: At diagnosis the median age was 58 yrs. (IQR 51-65), all were in the chronic phase and 86% had intermediate-higk risk Sokal score. First line treatment was Imatinib in 11, Dasatinib 9, and Nilotinib 7. 5 patients required a second line with Nilotinib, only one of them was considered to have failed first line. 17 discontinuations were performed as a planned physician strategy, 6 were carried out by patient's decision, 3 were forced by toxicities and in one case it was carried out to search for a pregnancy. Median time on TKIs before discontinuation was 73 months (IQR 59-135) and median time in RMM before TFR was 46 moths (IQR 35-71). Due to its retrospective nature, many patients did not have exact information on MR4.5 achievement date, since it was not available in Colombia until 2016. At a median follow-up of 12.5 months (IQR 4-20), 22 (81%) patients remain on TFR. As has been previously described most patients lost MMR in the first 6 months (median time to restart TKI 6 months; IQR 2-10). Only 1 patient did not achieve the MMR after TKI reinitiated, no progressions to accelerated or blastic phase were reported. 3 patients reinitiated the same ITK and 2 changed to another. 1 patient that was initially treated with Imatinib was changed to Nilotinib after reinitiation and after 2 years in MMR 4.5 has again discontinued TKI and has not lost response after 3 months. 9 (33%) patients developed withdrawal syndrome in most cases (7) with mild symptoms, only 2 had moderate symptoms. The estimated savings on TKIs for Colombian health care system for this patients are US$1.156.937, it is calculated that the cost of the PCR analysis performed for this patients to monitor TFR safely was US$35019. CONCLUSIONS: TKI has change the landscape for CML patients, that currently have a life expectancy similar to the general population; however, indefinitely treatment is associated with significant toxicities and a very high cost for the systems. TFR has become a real goal for a selected group of patients with CML. This report represents real-world data in Colombia, showing its feasibility and safety under well-controlled settings. Also, the estimated savings for a health care system of a middle-income country as Colombia are very significant, which is an additional support to insist with the decision makers of the system in the importance of the optimal access to TKIs and the necessary tests so that a greater number of patients can reach the necessary goals for a safe TFR. Figure 1 Figure 1. Disclosures Abello: Janssen: Honoraria; Amgen: Honoraria; Dr Reddy's: Research Funding. Sossa: Amgen: Research Funding.

scholarly journals Current and Emerging Pharmacotherapeutic Options for Smoking Cessation

2013 ◽  
Vol 7 ◽  
pp. SART.S8108 ◽  
Author(s):  
Kristin V. Carson ◽  
Malcolm P. Brinn ◽  
Thomas A. Robertson ◽  
Rachada To-A-Nan ◽  
Adrian J. Esterman ◽  
...  
Keyword(s):  
Developing Countries ◽  
Smoking Cessation ◽  
Clinical Practice ◽  
Chronic Disease ◽  
Developed Countries ◽  
Mental Illnesses ◽  
Current Clinical Practice ◽  
Efficacy And Safety ◽  
First Line ◽  
Marginalized Groups

Tobacco smoking remains the single most preventable cause of morbidity and mortality in developed countries and poses a significant threat across developing countries where tobacco use prevalence is increasing. Nicotine dependence is a chronic disease often requiring multiple attempts to quit; repeated interventions with pharmacotherapeutic aids have become more popular as part of cessation therapies. First-line medications of known efficacy in the general population include varenicline tartrate, bupropion hydrochloride, nicotine replacement therapy products, or a combination thereof. However, less is known about the use of these products in marginalized groups such as the indigenous, those with mental illnesses, youth, and pregnant or breastfeeding women. Despite the efficacy and safety of these first line pharmacotherapies, many smokers continue to relapse and alternative pharmacotherapies and cessation options are required. Thus, the aim of this review is to summarize the existing and developing pharmacotherapeutic and other options for smoking cessation, to identify gaps in current clinical practice, and to provide recommendations for future evaluations and research.

scholarly journals OP0163 COMPARATIVE ANALYSIS OF ETANERCEPT BIOSIMILAR AND ORIGINATOR USE IN CLINICAL PRACTICE: DATA FROM THE GERMAN BIKER-REGISTRY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 98.1-98
Author(s):  
G. Horneff ◽  
D. Windschall ◽  
T. Hospach ◽  
S. Mrusek ◽  
M. Rühlmann ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Adverse Events ◽  
Disease Activity ◽  
Special Interest ◽  
Global Assessment ◽  
Drug Exposure ◽  
Disease Onset ◽  
Injection Site Reaction ◽  
Physician Global Assessment ◽  
First Line

Background:In 2017, 2 Etanercept biosimilars became approved. Comparative studies performed in adult patients with rheumatoid arthritis, ankylosing spondylitis or psoriasis by extrapolation led to approval for juvenile idiopathic arthritis (JIA).Objectives:So far there is limited experience with Etanercept biosimilars in JIA: The large national data base of the BIKER-registry was used to describe experience with Etanercept biosimilars in clinical practice.Methods:In this retrospective analysis patients exposed to ETA were identified in the German BIKER-registry and grouped into cohorts according to initiation of treatment after 2017, use of the originator and of biosimilars. The course of JADAS10, Physician global assessment VAS 0–100-mm, Parent/patient global assessment VAS 0–100-cm, Active joint count 0-71, truncated at 10, ESR and CHAQ-DI was analyzed. Descriptive statistics was used for demographic, clinical data, drug exposure, adverse events (AEs) and events of special interest (ESI).Results:Until 31.10.2020, 2917 JIA patients were reported to have received Etanercept. Since January 1 2017, in 39 centres treatment with Etanercept was started in 439 patients (377 (85.9%) started with the originator and 62 (14.1%) started a Biosimilar). Biosimilars were prescribed n 17 centres (44%). In 12 centres (31%), Etanercept biosimilars were used first line in 62 patients. In 17 centres (44%), 63 patients switched for the originator to a biosimilar. 3 patients reswitched from the biosimilar to the originator. 4 patient switched from a biosimilar to the originator). 22 centres (56%) had not prescribed a biosimilars so far.In not a single centre, initiation of a biosimilar was more frequent than of the originator.The patients’ characteristics and disease activity parameters were widely comparanble. Patients receiving biosimilar first line were slightly older at disease onset and had a longer disease duration. Patients receiving biosimilar first line had more often rheumatoid factor (RF) negative polyarthritis while extended oligoarthritis was more frequent in the originator cohort. In the switching cohort, more patients had extended oligoarthritis and fewer had RF negative polyarthritis and ERA JIA.No difference in disease activity parameters was noted, neither at baseline, during the course of treatment nor at last observation upon treatment. A decrease of the JADAS10 indicates improvement in both groups (Figure 1). At the time of switching, 68% had JADAS minimal disease activity (MDA) and 43% were in JASDAS remission. At month 6 and 12 these numbers increased to 74%/65% and 62%/50%.In total, 66 adverse events (AE) were reported in 45 patients upon biosimilar treatment.33 patients had 1, 5 patients 2, 5 patients had 3 and 2 reported 4 events. Adverse event of special interest were hypersensitivity n=1, injection site reaction n=1, new onset of psoriasis n=1, celiac disease n=1, Crohn‘s diesease n=1, elevated transaminases n=2, depression n=1 and disease deterioration (arthritis flare) in n=21. In 20 patients, the etanercept biosimilar was discontinued.Conclusion:This analysis is the first attempt to present a large data sample on JIA patients exposed to Etanercept biosimilars. Biosimilar were used in a minority of patients and by a minority of centers although no difference in efficacy or safety was noted from our analysis. Until today, the use of the originator is by far exceeding the use of biosimilars. The prescription of a biosimilar either first line or by switching from the originator is limited to a part of centres. Differences in efficacy between first line biosimilar users and originator users could not be observed. Also, after switching, no loss of efficacy was observed.Disclosure of Interests:Gerd Horneff Speakers bureau: Pfizer, Daniel Windschall: None declared, Toni Hospach: None declared, Sonja Mrusek: None declared, Michael Rühlmann: None declared, Ariane Klein: None declared

scholarly journals Switching first-line targeted therapy after not reaching low disease activity within 6 months is superior to conservative approach: a propensity score-matched analysis from the ATTRA registry

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Lucie Nekvindová ◽  
Jiří Vencovský ◽  
Karel Pavelka ◽  
Pavel Horák ◽  
Zlatuše Křístková ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Targeted Therapy ◽  
Propensity Score ◽  
Disease Activity ◽  
Treatment Response ◽  
Daily Clinical Practice ◽  
Current Therapy ◽  
First Line ◽  
Treatment Target ◽  
Low Disease Activity

Abstract Background Treat-to-target (T2T) is a widely accepted strategy for patients with rheumatoid arthritis (RA). It recommends attaining a goal of at least low disease activity (LDA) within 6 months; otherwise, the current therapy should be modified. We aimed to investigate whether switching a first-line targeted therapy (TT) in patients not reaching LDA within 6 months leads to a higher probability of meeting LDA at the 12-month visit in daily clinical practice using data from Czech registry ATTRA. Methods We included patients with RA starting the first-line TT from 1 January 2012 to 31 January 2017 with at least 1-year follow-up. We created four mutually exclusive cohorts based on (1) switching to another TT within the first year and (2) reaching a treatment target (DAS28-ESR ≤ 3.2) at the 6-month visit. The primary outcome was the comparison of odds for reaching remission (REM) or LDA at the 12-month visit between patients switching and not switching TT after not reaching treatment target at 6 months. Before using logistic regression to estimate the odds ratio, we employed the propensity score to match patients at the 6-month visit. Results A total of 1275 patients were eligible for the analysis. Sixty-two patients switched within the first 5 months of the treatment before evaluating treatment response at the 6-month visit (C1); 598 patients reached the treatment target within 6 months of therapy (C2); 124 patients did not reach treatment response at 6-month visit and switched to another therapy (C3), and 491 patients continued with the same treatment despite not reaching LDA at the 6-month visit (C4). We matched 75 patients from cohort C3 and 75 patients from C4 using the propensity score. Patients following the T2T principle (C3) showed 2.8 (95% CI 1.4–5.8; p = 0.005) times increased likelihood of achieving REM/LDA at the 12-month visit compared to patients not following the T2T strategy (C4). Conclusions In daily clinical practice, the application of the T2T strategy is underused. Switching TT after not reaching REM/LDA within the first 6 months leads to a higher probability of achieving REM/LDA in RA patients at the 12-month visit.

scholarly journals Prevention of Hypotension following Spinal Anaesthesia in Caesarean Section - then and now

2012 ◽  
Vol 8 (4) ◽  
pp. 415-419
Author(s):  
J K Mitra
Keyword(s):  
Risk Factors ◽  
Clinical Practice ◽  
High Risk ◽  
Caesarean Section ◽  
Spinal Anaesthesia ◽  
Limited Data ◽  
First Line ◽  
High Risk Patients ◽  
Risk Patients ◽  
Poor Efficacy

Hypotension during spinal anaesthesia for caesarean section remains a common scenario in our clinical practice. Certain risk factors play a role in altering the incidence of hypotension. Aortocaval compression counteraction does not help to prevent hypotension. Intravenous crystalloid prehydration has poor efficacy; thus, the focus has changed toward co-hydration and use of colloids. Phenylephrine is established as a first- line vasopressor, although there are limited data from high-risk patients. Ephedrine crosses the placenta more than phenylephrine and cause possible alterations in the foetal physiology.http://dx.doi.org/10.3126/kumj.v8i4.6242 Kathmandu Univ Med J 2010;8(4):415-19   

Incorporation of plasma-based next-generation sequencing to improve guideline-concordant molecular testing in patients with newly diagnosed metastatic nonsquamous non-small cell lung cancer.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 14-14
Author(s):  
Charu Aggarwal ◽  
Melina Elpi Marmarelis ◽  
Wei-Ting Hwang ◽  
Dylan G. Scholes ◽  
Aditi Puri Singh ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Practice Change ◽  
Molecular Testing ◽  
Tier 2 ◽  
Newly Diagnosed ◽  
Next Generation ◽  
First Line ◽  
Tier 1 ◽  
Tier 3 ◽  
The Impact

14 Background: Current NCCN guidelines recommend comprehensive molecular profiling for all newly diagnosed patients with metastatic non-squamous NSCLC to enable the delivery of personalized medicine. We have previously demonstrated that incorporation of plasma based next-generation gene sequencing (NGS) improves detection of clinically actionable mutations in patients with advanced NSCLC (Aggarwal et al, JAMA Oncology, 2018). To increase rates of comprehensive molecular testing at our institution, we adapted our clinical practice to include concurrent use of plasma (P) and tissue (T) based NGS upon initial diagnosis. P NGS testing was performed using a commercial 74 gene assay. We analyzed the impact of this practice change on guideline concordant molecular testing at our institution. Methods: A retrospective cohort study of patients with newly diagnosed metastatic non-squamous NSCLC following the implementation of this practice change in 12/2018 was performed. Tiers of NCCN guideline concordant testing were defined, Tier 1: complete EGFR, ALK, BRAF, ROS1, MET, RET, NTRK testing, Tier 2: included above, but with incomplete NTRK testing, Tier 3: > 2 genes tested, Tier 4: single gene testing, Tier 5: no testing. Proportion of patients with comprehensive molecular testing by modality (T NGS vs. T+P NGS) were compared using one-sided Fisher’s exact test. Results: Between 01/2019, and 12/2019, 170 patients with newly diagnosed metastatic non-Sq NSCLC were treated at our institution. Overall, 98.2% (167/170) patients underwent molecular testing, Tier 1: n = 100 (59%), Tier 2: n = 39 (23%), Tier 3/4: n = 28 (16.5%), Tier 5: n = 3 (2%). Amongst these patients, 43.1% (72/167) were tested with T NGS alone, 8% (15/167) with P NGS alone, and 47.9% (80/167) with T+P NGS. A higher proportion of patients underwent comprehensive molecular testing (Tiers 1+2) using T+P NGS: 95.7% (79/80) compared to T alone: 62.5% (45/72), p < 0.0005. Prior to the initiation of first line treatment, 72.4% (123/170) patients underwent molecular testing, Tier 1: n = 73 (59%), Tier 2: n = 27 (22%) and Tier 3/4: n = 23 (18%). Amongst these, 39% (48/123) were tested with T NGS alone, 7% (9/123) with P NGS alone and 53.6% (66/123) with T+P NGS. A higher proportion of patients underwent comprehensive molecular testing (Tiers 1+2) using T+P NGS, 100% (66/66) compared to 52% (25/48) with T NGS alone (p < 0.0005). Conclusions: Incorporation of concurrent T+P NGS testing in treatment naïve metastatic non-Sq NSCLC significantly increased the proportion of patients undergoing guideline concordant molecular testing, including prior to initiation of first-line therapy at our institution. Concurrent T+P NGS should be adopted into institutional pathways and routine clinical practice.

scholarly journals The first-line therapy of aggressive non-Hodgkin’s lymphomas in russian clinical practice: data from the EQUILIBRIUM study

2020 ◽  
Vol 15 (2) ◽  
pp. 10-18
Author(s):  
L. G. Babicheva ◽  
I. V. Poddubnaya
Keyword(s):  
Overall Survival ◽  
Clinical Practice ◽  
Complete Remission ◽  
B Cell ◽  
Long Term Results ◽  
First Line ◽  
Therapy Efficacy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Hodgkin's Lymphomas

The objective: evaluation of effectiveness of the first-line therapy with rituximab of B-cell lymphoproliferative diseases in Russian clinical practice in the period from 2014 to 2017.Materials and methods. The EQUILIBRIUM post-registration multicenter study included 1000 patients aged 21 to 91 years old with a verified diagnosis of B-cell non-Hodgkin’s lymphoma, or chronic lymphocytic leukemia, who received at least 4 cycles of rituximab-containing therapy with Acellbia®. The group of aggressive non-Hodgkin’s lymphomas (aNHL), which is the subject of this article, included 295 patients with a median age of 55.9 years: diffuse B-large cell lymphoma – 87 %, primary mediastinal lymphoma – 11 %, Burkitt’s lymphoma – 1 %. Group characterized by the presence of aggressive clinical signs reflecting the poor prognosis: in the majority of patients, generalized stages were diagnosed (61 %), in half of the cases (50.2 %), extranodal localization of tumor foci was detected (in 32.4 % of patients there were 2 or more). The overwhelming majority of patients (84.5 %) received adequate treatment complying with national and international recommendations (R-CHOP, R-CHOEP and R-EPOCH, high-intensity NHL-BFM-R, R-HyperCVAD and R-MACOP-B regimes). The use of R-CVP, FCR, RB, Chl-R, R-monotherapy treatment programs (which received 15.5 % of patients) was considered inadequate for this category of patients.Results. According to the results of the final assessment, high therapy efficacy was established: the overall response exceeded 90 %, complete remission was achieved in most patients with aNHL (68.5 %), partial remission – in every 5th patient (21.8 %). With a median follow-up of 15 months, 16 (5.42 %) deaths and 34 (11.53 %) events were registered. Median of event-free survival and overall survival have not been achieved. Statistically significant differences depending on first-line therapy efficacy were found in overall survival (p = 0.00000) and eventfree survival (p = 0.00000), once again confirming that the main goal of aNHL treatment is to achieve complete remission.Conclusion. Available and compliant with national clinical guidelines treatment of aNHL patients with Russian bioanalogue of anti-CD20 monoclonal antibodies (Acellbia®) demonstrates high immediate efficacy and acceptable long-term results, comparable to a retrospective analysis of previous clinical studies of the original drug rituximab.

scholarly journals High-Dose Chemotherapy with Bendamustin and Melphalan Improves the Rate of Complete Remission in Myeloma Patients in First Remission Compared to Standard Melphalan Alone

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 39-40
Author(s):  
Sarah Farag ◽  
Ulrike Bacher ◽  
Myriam Legros ◽  
Daniel Betticher ◽  
Jean-Marc Lüthi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Complete Remission ◽  
Median Time ◽  
Maintenance Treatment ◽  
Induction Treatment ◽  
High Dose ◽  
First Line ◽  
Term Survival ◽  
Pulmonary Failure

Introduction: Consolidation of first-line induction treatment in myeloma (MM) patients (pts) with 200 mg/m2 melphalan chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) was established as standard of care three decades ago. However, definite cure in myeloma patients remains exceptional due to residual disease escaping intensive treatment, and almost all patients will ultimately relapse at earlier or later time points following ASCT. Thus, improving efficacy of HDCT in MM remains an unresolved issue. Methods: We performed a phase-II randomized trial comparing standard 200 mg/m2 Melphalan (Mel) HDCT to experimental HDCT treatment with 200 mg/m2 bendamustine, a bifunctional alkylating agent, given at days -4 and -3, combined with 200 mg/m2 melphalan split on days -2 and -1 at 100 mg/m2 (BenMel) before ASCT in MM pts. Patients had up to four cycles of first-line induction treatment with bortezomib, lenalidomide and dexamethasone. After ASCT, pts received lenalidomide maintenance treatment for two years. The primary endpoint was to show a 15% improvement of the rate of complete remission (sCR+CR) after HDCT with BenMel compared to Mel alone. MRD assessment from the bone marrow was performed by multiparameter flow cytometry after hematological engraftment following HDCT/ASCT. MRD negativity was defined as clonal plasma cells below 10(-5). Results: We randomized 120 myeloma pts (60 patients in each arm), with high-risk genetic abnormalities present in 21.3% of the patients. The median age was 63 years (range 35-74). The sCR/CR rate after ASCT before initiation of lenalidomide maintenance treatment was better in the BenMel arm compared to Mel alone (70.0% vs 51.7%; p=.039). The post-ASCT remission rates in detail were sCR 40.0% vs 31.7% (p=.341); CR 30.0% vs 20.0% (p=.205); VGPR 16.7% vs 33.3% (p=.035); and PR 13.3% vs 15.0% (p=.793). MRD negativity assessed in the bone marrow by flow cytometry was observed in 26 (45.6%) of the BenMel treated pts compared to 22 (37.9%) of the Mel pts. Median time until neutrophil engraftment was 11 days after BenMel vs 12 days after Mel (p=.096), and median time until platelet engraftment was 13 days in both arms (p=0.367); all pts had full engraftment of both cell lineages. Prolonged hospitalization duration was seen in BenMel pts (median 19 vs 18 days; p=.006) due to the longer BenMel treatment administration. Fully reversible acute renal insufficiency occurred in three (5%) BenMel pts compared to none of the Mel pts (p=.250). No treatment-related mortality was seen in both groups. ICU admissions were necessary in 3 pts (5%) in the BenMel group (ARDS, septic shock, pulmonary failure), and 2 Mel treated pts (3.3%; due to pulmonary failure and decompensated cardiomyopathy). The PFS rates at 12 months were 95% in BenMel pts and 91% in Mel treated pts (p=.551). OS at 12 months was 96% for both groups (p=.262), and median PFS and OS were not reached in both groups. Conclusions: Our data confirm that high-dose bendamustine combined with melphalan HDCT before ASCT in MM patients is safe and well tolerated. In particular, bendamustine-associated renal toxicity was manageable and reversible in all patients, and hematopoietic engraftment was comparable to standard melphalan HDCT. HDCT with BenMel improves the sCR/CR rate compared to standard melphalan alone. Thus, BenMel HDCT before ASCT warrants further investigation aiming to improve the long-term survival rates of MM patients, eventually combined with new maintenance strategies in the post-transplant period. Figure 1 Disclosures No relevant conflicts of interest to declare.

scholarly journals Selecting the first line treatment in non-metastatic hepatocellular carcinoma - comparing clinical practice guidelines

2020 ◽  
Vol 14 (2) ◽  
Author(s):  
Soumya Jogi ◽  
Radha Varanai ◽  
Sravani S. Bantu ◽  
Ashish Manne
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Practice ◽  
Systemic Therapy ◽  
Residual Disease ◽  
Disease Process ◽  
Locoregional Therapy ◽  
Line Treatment ◽  
First Line ◽  
Tumor Boards ◽  
First Line Treatment

Primary malignancy of the liver or hepatocellular carcinoma (HCC) is unique in its presentation, disease process, and management. Unlike breast or colon cancer, the staging of HCC depends on performance status and baseline liver function along with pathological characteristics. Apart from traditional options like surgery and systemic therapy, effective management can be achieved in selected cases with liver transplant and locoregional therapy (LRT) like transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and ablation. Liver study societies and cancer groups across the globe proposed guidelines to aid the treating physicians in choosing first-line treatment for liver cancer. It is tough to compare these guidelines as they differ not only in treatment recommendations but also in risk assessment (and staging). The approach to the same patient may be different in the country he or she is managed. In clinical practice, decisions are usually taken on the consensus of multidisciplinary tumor boards and do not necessarily adhere to any guidelines. In the early (and very early) stage HCC, curative options like surgery, transplant, and ablation are recommended. In intermediate stage HCC, LRT (TACE and TARE) is preferred in the first line and systemic therapy for treatment failure or residual disease. Systemic therapy, including the atezolizumab/bevacizumab combination and tyrosine kinase inhibitors (TKI) like sorafenib and lenvatinib, is used for advanced stages. Supportive care is advised for terminal stage HCC.

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